The objective of the research is to gain further understanding of the biochemical bases of kidney function, and of the biochemical mechanisms of action of certain drugs and hormones on these functions. During the coming year we expect to work in the following areas: Explore further the sites and mechanisms of action of several diuretics with the aim of furthering our knowledge of the biochemical factors regulating sodium and potassium transport in the kidney. Examine: 1) the modification of renal responses to hormones by substances which inhibit endogenous cyclic AMP and cyclic GMP egress from the renal cell; 2) the excretion and metabolism of (C14) dibutyryl cyclic AMP by the isolated kidney; 3) the role of chlorpropamide in regulating cyclic nucleotide concentrations and protein kinase activity in the isolated perfused rat kidney. Investigate factors altering metabolism of endogenous lipids of the kidney. Re-examine gluconeogenesis and ammoniagenesis with the aim of determining metabolite levels in distinct anatomical zones of kidneys undergoing different rates of gluconeogenesis and ammoniagenesis. BIBLIOGRAPHIC REFERENCES: Bowman, R.H.: Renal secretion of (S35) furosemide and its depression by albumin binding. Am. J. Physio. 229: 93-98, 1975. Bowman, R.H.: The perfused rat kidney; in Methods in Enzymology (ed. by J.C. Hardman and B.W. O'Malley), Academic, New York, 0975. Vol. XXXIX, pp 3-11.